Necrotizing enterocolitis (NEC) is a condition primarily seen in premature infants and occurs when portions of the bowel undergo necrosis (tissue death). Initial symptoms include feeding intolerance, abdominal distension and bloody stools. Symptoms may progress rapidly to abdominal discoloration with intestinal perforation and peritonitis and systemic hypotension requiring intensive medical support, including surgery.
The diagnosis of NEC is usually suspected clinically but often requires the aid of diagnostic imaging modalities such as x-ray. Radiographic signs of NEC include dilated bowel loops, paucity of gas, a “fixed loop” (unaltered gas-filled loop of bowel), pneumatosis intestinalis, portal venous gas, and pneumoperitoneum (“free air” outside the bowel within the abdomen). Recently ultrasonography has proven to be useful as it may detect signs and complications of NEC before they are evident on radiographs.
Current treatment consists primarily of supportive care including providing bowel rest by stopping oral or enteral feeding, gastric decompression with intermittent suction, fluid administration to correct electrolyte imbalances, support for blood pressure, parenteral nutrition, and antibiotic therapy. Where the disease is not halted through medical treatment alone, or when the bowel perforates, immediate emergency surgery to remove the dead bowel is generally required. Surgery may require a colostomy, which may be able to be reversed at a later time. Some children may suffer later as a result of short bowel syndrome if extensive portions of the bowel are removed.
NEC has no definitive known cause. An infectious agent has been suspected, but no common organism has been identified during cluster outbreaks in neonatal hospital units, although Pseudomonas aeruginosa is suspected of causing NEC. Other factors may be involved. The most common area of the bowel affected by NEC is near the ileocecal valve (the site of transition between the small and large bowel). NEC is almost never seen in infants before oral feedings are initiated. Formula feeding increases the risk of NEC by tenfold compared to infants who are fed breast milk alone.
Once an infant is born prematurely, thought must be given to decreasing the risk for developing NEC. Toward that aim, the methods of providing hyperalimentation and oral feedings are both important. A recent study, Drenckpohl, D., et al. (Pediatrics, 2008, 122; 743-751) demonstrated that using a higher rate of lipid (fats and/or oils) infusion for very low birth weight infants in the first week of life resulted in zero infants developing NEC in the experimental group, compared with 14% with NEC in the control group. These finding demonstrate that prevention of NEC is possible.
Typical recovery from NEC if medical, non-surgical treatment succeeds, may take 10-14 days or more without oral intake and then demonstrated ability to resume feedings and gain weight. Recovery from NEC alone may be compromised by co-morbid conditions that frequently accompany prematurity. Long term complications of medical NEC include bowel obstruction and anemia. Despite a significant mortality risk, long-term prognosis for infants undergoing NEC surgery is improving, with survival rates of 70-80%. However, infants who do survive surgery for NEC are at-risk for complications including short bowel syndrome and neuro-developmental disability.
A therapy that could prevent or treat NEC, especially one that could reduce or eliminate the need for surgical intervention, would have a major impact on the treatment, survival and long term health and development of these very ill infants. Accordingly, it is an object of the instant invention to provide such a treatment option.